Suppressive effects of zingerone on Polyphosphate-Mediated vascular inflammatory responses

Background and Objective: Human endothelial cells-derived polyphosphate (PolyP) is one of the pro-inflammatory mediators as suggested by the previous reports. Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to possess various pharmacological activities. This study was undertaken to investigate whether ZGR can modulate PolyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. Materials and Methods: After HUVECs or mice were activated with PolyP, cells or mice were post-treated with ZGR. The anti-inflammatory activities of ZGR were determined by measuring permeability, leukocytes adhesion and migration and activation of pro-inflammatory proteins in PolyP-activated HUVECs and mice. In addition, the beneficial effects of ZGR on survival rate in PolyP-injected mice. Statistical relevance was determined by one-way analysis of variance (ANOVA). P values less than 0.05 were considered to indicate significance. Results: It was found that ZGR inhibits PolyP-mediated barrier disruption, the expressions of cell adhesion molecules and leukocyte to HUVEC adhesion/migration. Interestingly, PolyP-induced NF-κB activation and the productions of TNF-α and IL-6 were inhibited by ZGR in HUVECs. These anti-inflammatory functions of ZGR were confirmed in PolyP injected mice. Conclusion: In conclusion, based on the anti-inflammatory effects of ZGR in PolyP-mediated septic response, ZGR have therapeutic potential for various systemic inflammatory diseases.